The invention relates to a method for determining properties of blood, such as the blood viscosity of a person.
Atherosclerosis is the most common disease in the western world and partly for this reason represents one of the greatest problems with which our health care services and our society in general are confronted. Since atherosclerosis is clearly related to age, the problems associated with atherosclerosis will only increase due to the increase in the ageing population in the western world. Atherosclerosis is a generalized disease which can manifest itself in the coronaries by means of acute heart death, myocardial infarction or disabling angina pectoris. Atherosclerosis in the head is responsible for the largest number of strokes. Not only does this cause mortality, but also a greater or lesser degree of permanent invalidity. Elsewhere in the blood vessels of the body atherosclerosis can be the cause of reduced blood circulation in the legs or in the kidneys. Thrombosis is found to play an essential part in the process of atherosclerosis and increasingly recognized recently is also the significant part which inflammatory processes can play in activating and perhaps sometimes also in causing atherosclerosis. Much atherosclerosis therapy therefore focuses on suppressing thrombosis. It has also been found that the presence of xe2x80x9cmarkersxe2x80x9d of inflammation (such as CRP and other active-phase-proteins) entails an increased chance of atherosclerotic complications. The present invention has for its object to provide a method which enables monitoring of thrombosis processes and/or the activity of atherosclerosis. The prevention of atherosclerotic complications can hereby be controlled better and the medicinal therapy (anti-thrombotic and anti-inflammatory) can be adapted thereto.
It is known that the risk of thrombosis and atherosclerotic complications increases with an increase in the viscosity of the blood. The taking of blood so as to determine the viscosity is however time-consuming and costly, particularly when this has to be determined over a longer time and regularly in order to monitor the risks for a patient. Furthermore, when blood is taken for examination in vitro, the viscosity and coagulation parameters of blood are influenced to a certain extent and do not therefore give an accurate representation of the properties of blood in vivo. They are also only random indications which can be influenced by many factors and thus provide only limited certainty that, if necessary, timely treatment can be undertaken as the risk increases.
The invention therefore has for its object to provide a method of the type specified in the preamble which at least reduces these drawbacks.
In the method according to the invention this object is achieved by generating in vivo for a determined time, by means of an electrical alternating current of a determined frequency, a measurement signal of the impedance of the blood between at least two points centrally in a blood volume, wherein the measurement signal is processed such that variations therein with a frequency in the order of magnitude of the heart frequency are substantially absent therefrom, and comparing the processed measurement signal with predetermined relations between impedance and the properties of the blood, such as the viscosity. A continuously determined impedance measurement signal varies with ambient parameters such as the flow speed. By eliminating the variations with a frequency in the order of magnitude of the heart frequency a reliable value is obtained for the actual blood properties such as the viscosity, and thus the risks for the patient.
An ECG signal is further measured in a cavity containing the blood volume and processing of the measurement signal occurs by only considering measurement values in the same phase as the ECG signal. The phase of the ECG signal corresponds to the maximal and/or minimal impedance. By measuring each time in the same phase of the heart rhythm, the conditions for the flow speed and the like are the same each time, so that the variations with the frequency of the heart rhythm are eliminated. The energy consumption is moreover low herein, so that the device can operate on batteries and can for instance be portable.
According to a further development of the invention a blood viscosity reducing agent is applied to the patient in a dosage such that the measured impedance is reduced to a predetermined value. Precise determining of the viscosity enables a good dosing of the agent.
The distance between the aforementioned two points centrally in the blood volume is a small fraction of the distance between the two points and the boundary of the blood volume. In this way, the measurement is influenced by surrounding tissue to a negligible extent at most.
A good measurement is obtained particularly when the aforementioned two points are located centrally in the right atrium of the heart of the patient is applied. The right-hand atrium is readily accessible for the measurement and comprises a suitably large volume of blood to enable a precise measurement.
The invention likewise relates to and provides a device for in vivo determining of determined blood properties, such as the blood viscosity of a person, comprising a catheter, which comprises at least two electrode systems close to a distal end and connecting lines extending from the electrode systems to the proximal end of the catheter, a measuring device which is connectable to the connecting lines and which is embodied such that it can generate a measurement signal of the impedance between the electrode systems, and a processing device which is embodied such that it processes the measurement signal such that variations therein with a frequency in the order of magnitude of the heart frequency are substantially absent therefrom.
According to a suitable embodiment the measuring unit of the device according to the invention is received in an implantable unit. After introduction into a patient the progress of the measured blood property can be monitored regularly for a longer period of time. The device according to the invention can however also be used for more short-term applications, for instance in the case of acute thrombotic events, in which case the measuring device and the processing device are received in housings which remain outside the body of the patient. The catheter introduced into the patient via a peripheral vein is connected to the measuring device.
According to a very suitable embodiment the measuring device is combined with an implantable heart pacemaker unit and provided with two electrically separated circuits each having an individual power source, wherein the one circuit is adapted for the pacemaker function and the other circuit is adapted for the impedance measurement.
Heart pacemakers are generally known. The pacemaker unit herein contains, as can also be the case in the invention, an electrical power supply generally in battery form and the electronics required for the pacemaker function. The pacemaker unit is further also often provided with read-out means so that radiographic data can be read out in order to enable monitoring of the operation of the pacemaker and thus also the patient. The pacemaker unit is generally implanted on the chest under the skin. The device according to the invention, whether or not combined with a heart pacemaker, can be introduced in the same manner.
An electric catheter, referred to as the xe2x80x9cleadxe2x80x9d in professional jargon, is fixed to the device according to the invention when it is implanted under the skin. This electric catheter is inserted into the bloodstream at a suitable location and guided via the bloodstream to the heart. One or more electrodes are then placed on the electric catheter, generally on the end thereof. Via these electrodes it is then possible to generate an electrical stimulus which supports the working of the heart. As is generally known, current pulses in the order of 5 mA for 0.5 ms are herein generally more than sufficient. In older models of pacemakers a stimulus signal is generated at a fixed frequency. In the pacemakers substantially employed nowadays, so-called xe2x80x9con demand pacemakersxe2x80x9d, a further sensor is however provided on the so-called lead. This sensor monitors whether the heart is functioning properly.
Subject to the sensor signal, the heart pacemaker unit will be able to decide whether or not a stimulus signal must be generated via a stimulating electrode. It is conceivable here for the sensor electrode and stimulating electrodes to be formed by one and the same electrode or to be integrated into one electrode.
It is per se known that blood has electrical properties and that these electrical properties are different for the plasma and the blood cells. The plasma and the interior of the blood cells consist of conductive fluids with a determined electrical resistance, and the cell membranes consist of phospholipids and proteins with dielectric properties. The electrical impedance of blood is thus primarily determined by three parameters: the plasma resistance, the interior resistance in the cell and the capacitance of the membrane.
The electrical impedance of blood is found to change in the presence of coagulation factors such as fibrinogen. The electrical impedance of blood is also found to be closely related to the erythrocyte sedimentation rate, which is a significant xe2x80x9cmarkerxe2x80x9d for the extent of an inflammatory process. A measured impedance of the blood can be related to a so-called thrombosis factor, which provides a measure for the tendency to thrombosis, and to a factor which indicates the extent of inflammation in atherosclerosis. These factors can then be linked to a medication to prevent these processes. The factors can then for instance be linked to a determined dosage of a particular medicine. It will be apparent that the measured impedance can optionally also be linked directly to a medication or a determined dosage of a particular medicine. It will generally be the case that the lower the intravascularly measured electrical resistance of the blood, the smaller the chance of thrombosis and the lower the inflammatory activity of the atherosclerosis. In addition, it will generally be the case that the chance of thrombosis increases when the measured electrical capacitance of the blood increases. It will however be apparent that these are basic principles, exceptions to which can be envisaged.
In accordance with a particular embodiment, the device according to the invention is further adapted to determine a factor subject to the measured impedance, which factor is a measure for the tendency to thrombosis and/or the device is further adapted to determine a factor subject to the measured impedance, which factor indicates the inflammatory activity in atherosclerosis.
By means of test measurements, for instance in a laboratory outside the human body, it is possible to determine a more or less precise relation between the electrical impedance of the blood on the one hand and the chance of thrombosis and/or the atherosclerotic activity on the other, in order to thus assign to this chance respectively activity a factor which will take on a greater value as the chance respectively activity increases (it should however be noted that it is also conceivable to have the value of the thrombosis factor decrease with the chance respectively activity).
According to the invention the impedance measurement can in particular relate to either a resistance measurement or a capacitance measurement or a phase difference measurement, or a combination of these. Which of these types of impedance measurement is applied can be patient-dependent and/or can depend on the type of thrombosis formation it is wished to monitor.
In order to prevent the impedance measurement possibly disrupting the actual pacemaker function, it is advantageous according to the invention when the device, if it is combined with a heart pacemaker unit, is provided with two electrically separated circuits each having an individual power source, wherein the one circuit is adapted for the pacemaker function and the other circuit is adapted for the intravascular impedance measurement.
It is particularly advantageous according to the invention when the intravascular part is embodied such that the at least two electrodes can be placed in the right-hand atrium of the heart for performing the impedance measurement. This is advantageous according to the invention because the electrodes will be placed as freely as possible in the blood without contact with other tissue, whereby the impedance of the blood per se is measured. For the connection between the pacemaker unit and the intravascular part with the electrodes for the intravascular impedance measurement it is important that this connection enables the transfer of signals between the pacemaker unit and the electrodes.
As it is of particular practical advantage when the electrical power supply is accommodated in the unit, as is usual as such in pacemakers, it is recommended that the connection be an electrical connection, in which case the device according to the invention will comprise a catheter, in professional jargon the so-called lead, which is connected on the one hand to the device and on the other to the intravascular part, wherein the intravascular part as such can form part of the catheter.
Taking this into consideration, the device according to the invention comprises in a preferred embodiment a catheter which comprises an intravascular part with at least two electrode systems for impedance measurement, is electrically connectable with one end to the pacemaker unit, and comprises one or more sensor electrodes and/or stimulating electrodes for the pacemaker function.
A further, more advantageous embodiment of the above described embodiment with electric catheter, intended for a device combined with a heart pacemaker, provides that the sensor electrodes and/or stimulating electrodes for the pacemaker function are arranged at the other end of the catheter, that the other end of the catheter is intended for placing in the apex of the right-hand ventricle, and that the distance between this other end of the catheter on the one hand and the intravascular part with the electrodes for the impedance measurement on the other is such that when the other end is placed in the apex of the right-hand ventricle, the intravascular part is situated in the right-hand atrium.
According to a further advantageous embodiment, the device is adapted to enable remote read-out of the determined factors of thrombosis formation and/or of inflammatory activity and/or the measured impedance values. This read-out can then take place on-line for instance for 24 to 48 hours, although read-out can also take place periodically, for instance once per week or per month.
The read-out of the thrombosis factors can then be carried out herein at longer intervals than the periodicity of the performance of the measurement. It can thus for instance be envisaged that once a day determined thrombosis factors are read out once per week or once per two weeks or once per month. That the device must be provided for this purpose with suitable memory means realizable with known means from the prior art will be apparent.
It is further pointed out that the determining of the stated factors can take place outside the implanted device. It is also conceivable to read out both the factors and the measured impedance values from which the factors are determined. Reading out can take place remotely with per se known techniques which are already known as such in the field of pacemakers.
It is possible here to envisage for instance radiographic read-out. According to the invention patients with a pacemaker are envisaged in the first instance, since most of these patients have atherosclerosis and the pacemaker system with its power source and its catheter (xe2x80x9cleadxe2x80x9d) in the bloodstream can thus be easily modified for an electric impedance measurement of the blood. According to the invention however, this impedance measurement technique can also be applied wholly separately of a pacemaker, permanently using a separate measuring device or temporarily via a catheter in a peripheral vein to the right-hand atrium, as described above for monitoring an anti-coagulation therapy in acute thrombotic events.